Kabara Cancer Research Institute, Gundersen Medical Foundation, La Crosse, Wisconsin, USA.
Division of Hematology & Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Dev Dyn. 2024 Jul;253(7):677-689. doi: 10.1002/dvdy.686. Epub 2023 Dec 23.
Growth factor receptor-bound 7 (Grb7) is an adaptor protein involved in signal transduction downstream of multiple receptor tyrosine kinases, including ERBB, FGFR, and PDGFR pathways. Experimental studies have implicated Grb7 in regulating cell proliferation, survival, migration, and invasion through its large repertoire of protein-protein interactions.
Here, we describe the generation and characterization of a Grb7 knockout mouse. These mice are viable and fertile. A lacZ knock-in reporter was used to visualize Grb7 promoter activity patterns in adult tissues, indicating widespread Grb7 expression in glandular epithelium, the central nervous system, and other tissues. The sole defect observed in these animals was a failure of Grb7 knockout females to successfully raise pups to weaning age, a phenotype that was independent of both paternal and pup genotypes.
These data suggest a regulatory role for Grb7 in mammary lactational physiology.
生长因子受体结合蛋白 7（Grb7）是一种衔接蛋白，参与多种受体酪氨酸激酶（包括 ERBB、FGFR 和 PDGFR 途径）下游的信号转导。实验研究表明，Grb7 通过其大量的蛋白质-蛋白质相互作用，参与调节细胞增殖、存活、迁移和侵袭。
在这里，我们描述了 Grb7 敲除小鼠的产生和特性。这些小鼠具有活力和生育能力。使用 lacZ 敲入报告基因来可视化成年组织中 Grb7 启动子活性模式，表明 Grb7 在腺上皮、中枢神经系统和其他组织中广泛表达。这些动物唯一观察到的缺陷是 Grb7 敲除雌性无法成功将幼崽抚养到断奶年龄，这种表型与父本和幼崽基因型均无关。
这些数据表明 Grb7 在乳腺泌乳生理学中起调节作用。
